The coordinated action of G-CSF and ELR + CXC chemokines in neutrophil mobilization during acute inflammation

Wengner, Antje M.; Pitchford, Simon; Furze, Rebecca C.; Rankin, Sara M.

doi:10.1182/blood-2007-07-099648

Cited by 197 publications

(218 citation statements)

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“…Our data indicate that Gr-1-positive cells become rapidly activated in response to stroke in the bone marrow, which causes the release of the CXCR2-positive myeloid population within 4 hours reperfusion. It has been shown that CXCL1 and G-CSF exert coordinated actions on neutrophil mobilisation from the bone marrow (Wengner et al, 2008). Although in our study CXCL1 was upregulated in bone marrow-derived neutrophils/monocytes after both sham and stroke surgery, our results indicate a more pronounced release of CXCL1 (at 4 hours reperfusion) and G-CSF (at 10 minutes reperfusion) into the circulation in response to stroke, which correlates with increased stroke-induced cell mobilisation from the bone marrow.…”

Section: Discussionmentioning

confidence: 99%

“…It is also known that humoural factors, including cytokines and chemokines are rapidly elevated in both the brain and the periphery after stroke (Offner et al, 2006a). In addition, we recently showed that cerebral ischaemia induces systemic upregulation of CXCL1 (KC), a chemokine that acts in concert with granulocyte-colony-stimulating factor (G-CSF) to mobilise neutrophils from the bone marrow in response to inflammatory challenges (Chapman et al, 2009;Wengner et al, 2008). The release of neutrophil granulocytes from the bone marrow is a complex process, which involves an antagonistic interaction between the neutrophil chemokine receptors CXCR2 and CXCR4 (Eash et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…The release of neutrophil granulocytes from the bone marrow is a complex process, which involves an antagonistic interaction between the neutrophil chemokine receptors CXCR2 and CXCR4 (Eash et al, 2010). Activation of CXCR2 by its ligands, CXCL1 and/or CXCL2, is a key step in neutrophil mobilisation and recruitment to inflamed tissues in various diseases, including arthritis, ischaemia-reperfusion injury, or inflammatory demyelination in the central nervous system (Jacobs et al, 2010;Li et al, 2010;Liu et al, 2010;Martin et al, 2003;von Vietinghoff et al, 2010;Wengner et al, 2008). Other chemokine receptors such as CCR5 can also interact with key leukocyte mobilisation responses and can promote the recruitment of monocytes, granulocytes, and T cells to the sites of inflammation (Balistreri et al, 2007;Honczarenko et al, 2002;Kohlmeier et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Experimental Stroke-Induced Changes in the Bone Marrow Reveal Complex Regulation of Leukocyte Responses

Dénes

McColl

Leow-Dyke

et al. 2010

J Cereb Blood Flow Metab

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Stroke induces a systemic response that involves rapid activation of inflammatory cascades, followed later by immunodepression. Experimental stroke-induced responses in the bone marrow, which is the primary source of circulating monocytes and granulocytes, have not been investigated previously. We show that cerebral ischaemia induced early (4 hours) release of CXCR2-positive granulocytes from the bone marrow, which was associated with rapid systemic upregulation of CXCL1 (a ligand for CXCR2) and granulocyte-colony-stimulating factor, a key cytokine involved in the mobilisation of bone marrow leukocytes. This process involves rapid activation of nuclear factor-jB and p38 mitogen-activated protein kinase in bone marrow myeloid cells. T-cell numbers in the bone marrow increased after stroke, and bone marrow cells did not show suppressed cytokine response to bacterial endotoxin stimulation in vitro. Stroke-induced laterality observed in the brain stem and in the bone marrow indicates direct involvement of the autonomic nervous system in stroke-induced cell mobilisation. We also show that systemic inflammatory changes and leukocyte responses in the bone marrow are profoundly affected by both anaesthetic and surgical stress. We conclude that stroke influences leukocyte responses in the bone marrow through multiple mechanisms and suggest that preclinical studies should take into consideration the effect of surgical manipulation in experimental models of stroke.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Experimental Stroke-Induced Changes in the Bone Marrow Reveal Complex Regulation of Leukocyte Responses

Dénes

McColl

Leow-Dyke

et al. 2010

J Cereb Blood Flow Metab

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“…In addition to its positive influence on granulopoiesis, G-CSF is a well-known disruptor of neutrophil retention 42 . G-CSF pressures the bone marrow to release neutrophils through thrombopoietin (TPO)-induced upregulation of CXCR2 ligands on megakaryocytes 38 , reduction of CXCL12 expression by bone marrow stromal cells 43,44 and downregulation of CXCR4 on neutrophils themselves 45 .…”

Section: Neutrophil Retention and Release From Bone Marrowmentioning

confidence: 99%

Neutrophils in cancer: neutral no more

2016

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SummaryNeutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view.The traditionally held belief that neutrophils are inert bystanders is being challenged by recent literature. Emerging evidence indicates that tumors manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumor behavior. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets. 2The name neutrophil -given to polymorphonuclear, granulocytic cells by Paul Ehrlich in the late 19th century -is based on the inability of these cells to retain acidic or basic dyes and for their preferential uptake of pH neutral dyes 1 . Although their neutral staining led to the identification of these cells, neutrophils in the cancer setting are anything but neutral.Neutrophils in tumor-bearing hosts can oppose or potentiate cancer progression. These two types of behavior are controlled by signals emanating from cancer cells or stromal cells within the tumor microenvironment, which educate neutrophils to execute the demise of the tumor or facilitate support networks that lead to its expansive spread. These functions can occur locally in or around the tumor microenvironment, as well as systemically in distant organs.Until the past few years, other immune cells such as macrophages have overshadowed the role of neutrophils in cancer. But recent studies and the development of new genetic tools have provided the cancer community with new insights into the profound influence of these dynamic cells by uncovering distinct capabilities for neutrophils throughout each step of carcinogenesis: from tumor initiation to primary tumor growth to metastasis.During these processes, neutrophils take on different phenotypes and sometimes opposing functions. Emerging evidence also indicates that these cells are highly influential, and are able to change the behavior of other tumor-associated cell types -primarily other immune cells. In this Review, we focus on how tumors manipulate the generation and release of neutrophils from the bone marrow. We discuss the mechanisms identified in animal models by which neutrophils participate in tumor initiation, growth and metastasis. Finally, we highlight the potential of these cells as clinical biomarkers and therapeutic targets. In humans, neutrophils are the most abundant immune cell population, representing 50-70% of all leukocytes. Over 10 11 neutrophils may be produced per day 2 , and tumors can increase this number by even more. Indeed, patients with various cancer types, including but not limited to breast, lung and colorectal cancer, often exhibit increased numbers of circulating neutrophils 3,4 . Recent studies have identified key pathways that tumors exploit to disrupt normal neutrophil homeostasis and these are discuss...

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“…An array of chemokines is induced by inflammation and recruits monocytes, neutrophils and other cells to sites of infection. The chemokine receptors CCR2 and CXCR2 are required for monocytes and neutrophils, respectively, to egress from the bone marrow into the blood during steady state and infection [7][8][9][10]. They are also central for monocyte and neutrophil recruitment and host survival during infections [9,[11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Monocyte and neutrophil recruitment during oral Salmonella infection is driven by MyD88‐derived chemokines

Rydström

Wick

2009

Eur J Immunol

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Oral Salmonella infection recruits phagocytes to Peyer's patches (PP) and MLN. The chemokines induced in infected PP and MLN, the cellular sources during infection and the TLR signaling pathways involved in vivo are not known. Here, we show that CCL2, CXCL9 and CXCL2 mRNA are up-regulated in PP and MLN coincident with the first arrival of monocytes and neutrophils. Laser capture microdissection microscopy revealed that chemokine mRNA up-regulation was differently distributed in PP. Despite this, recruited monocytes and neutrophils formed inflammatory cell clusters throughout PP. Monocytes and neutrophils purified from infected mice preferentially produced CXCL2 and small amounts of CCL2, and neutrophils from infected mice migrated towards CXCL2 and CCL3. Furthermore, phagocyte recruitment to PP and MLN was intact in mice lacking TLR4 alone and when signaling through TLR4 and TLR5 was simultaneously absent; however, recruitment was compromised in MyD88 À/À and more so in MyD88 À/À TLR4 À/À double knockout mice. Phagocyte release into the blood, however, was only marginally reduced in MyD88 À/À TLR4 À/À mice. Defective phagocyte recruitment to PP and MLN of MyD88 À/À TLR4 À/À mice was paralleled by low chemokine induction. These data provide insight into the chemokines and TLR signaling pathways that orchestrate the early phagocyte response to oral Salmonella infection.Key words: Chemokine . Monocyte . Salmonella . TLR IntroductionMonocytes and neutrophils are critical in the first line of defense against bacteria. They develop in the bone marrow, are released into the circulation and enter tissues in response to infection. Murine monocytes in the blood are a heterogeneous population and have been divided into two main subsets based on whether they are present in steady state or recruited under inflammatory conditions [1]. Inflammatory Gr-1 hi CCR2 hi CX 3 CR1 low monocytes, which have also been called TipDC upon entering a tissue, are a source of molecules important in controlling bacterial infection, particularly iNOS and TNF-a [2][3][4].Salmonella enterica serovar Typhimurium (S. typhimurium) is a Gram-negative facultative intracellular bacterium that infects via the oral route. Orally acquired Salmonella exits the gut lumen primarily by crossing the follicle-associated epithelium overlying Peyer's patches (PP) via M cells (reviewed in [5]). The bacteria are then further spread to the MLN, most likely by DC, and to the spleen and liver via the blood [5,6]. After oral infection with S. typhimurium, neutrophils and Gr-1 hi CCR2 hi inflammatory monocytes accumulate in PP and MLN, the first organs encountering the bacteria, beginning 2-3 days after infection [3].Chemokines are the main mediators involved in the recruitment and migration of leukocytes to and within tissues. An array of chemokines is induced by inflammation and recruits monocytes, neutrophils and other cells to sites of infection. The chemokine receptors CCR2 and CXCR2 are required for monocytes and neutrophils, respectively, to egress from the bone ...

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The coordinated action of G-CSF and ELR + CXC chemokines in neutrophil mobilization during acute inflammation

Cited by 197 publications

References 63 publications

Experimental Stroke-Induced Changes in the Bone Marrow Reveal Complex Regulation of Leukocyte Responses

Experimental Stroke-Induced Changes in the Bone Marrow Reveal Complex Regulation of Leukocyte Responses

Neutrophils in cancer: neutral no more

Monocyte and neutrophil recruitment during oral Salmonella infection is driven by MyD88‐derived chemokines

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